Vaginal colonization of women after oral administration of Lactobacillus crispatus strain NTCVAG04 from the human microbiota.

BACKGROUND: The genomic approach has deeply changed the microbiology perspective, mainly concerning the microbioma identification. In this regard, some microbes colonize the healthy vagina. Vaginitis is a common gynecological ailment and includes bacterial vaginosis (BV), usually caused by local dysbiosis, such as a microbiota imbalance. Lactobacilli are the most prevalent bacteria colonizing the healthy vagina, so guaranteeing local eubiosis. In particular, vaginal colonization by L. crispatus is associated with low susceptibility to BV. Therefore, probiotics, such as life bacteria providing health advantages, are a current strategy in the prevention or treatment of vaginitis, including BV. However, there is a low level of evidence that probiotics after ingestion could really colonize the vagina. In particular, no study evidenced that L. crispatus after ingestion can colonize vagina. Therefore, the current study explored the capacity of Biovaginil® (NTC, Milan, Italy) dietary supplement containing Lactobacillus crispatus NTCVAG04 and vitamin A to colonize the gut and vagina in women with a history of vaginitis/vaginosis. METHODS: Twenty fertile females (mean age 34.0 years) were enrolled in the study. Rectal and vaginal swabs were collected at baseline and after the first and second cycle of Biovaginil®. Each cycle lasted 14 days within two consecutive menstrual periods. RESULTS: Seven women were excluded from the analysis because the samples were technically not evaluable. One woman dropped out because of mild adverse event. At the end of the study, nine women (75%) had positive rectal swab for L. crispatus NTCVAG04, and 8 of them also had positive vaginal swab. CONCLUSIONS: The current study provided the first evidence that L. crispatus NTCVAG04, administered by two Biovaginil® courses, colonized both the gut and vagina. Moreover, the L. crispatus NTCVAG04 strain could be considered the archetype of a new class of oral probiotics that actively colonize the vagina, and that could be called "colpobiotics."

Expression of Genes for Drug Transporters in the Human Female Genital Tract and Modulatory Effect of Antiretroviral Drugs.

Anti-retroviral (ARV) -based microbicides are one of the strategies pursued to prevent HIV-1 transmission. Delivery of ARV drugs to subepithelial CD4+ T cells at concentrations for protection is likely determined by drug transporters expressed in the cervicovaginal epithelium. To define the role of drug transporters in mucosal disposition of topically applied ARV-based microbicides, these must be tested in epithelial cell line-based biopharmaceutical assays factoring the effect of relevant drug transporters. We have characterised gene expression of influx and efflux drug transporters in a panel of cervicovaginal cell lines and compared this to expression in cervicovaginal tissue. We also investigated the effect of dapivirine, darunavir and tenofovir, currently at advanced stages of microbicides development, on expression of drug transporters in cell lines. Expression of efflux ABC transporters in cervical tissue was best represented in HeLa, Ect1/E6E7 and End1/E6E7 cell lines. Expression of influx OCT and ENT transporters in ectocervix matched expression in Hela while expression of influx SLCO transporters in vagina was best reflected in VK2/E6E7 cell line. Stimulation with darunavir and dapivirine upregulated MRP transporters, including MRP5 involved in transport of tenofovir. Dapivirine also significantly downregulated tenofovir substrate MRP4 in cervical cell lines. Treatment with darunavir and dapivirine showed no significant effect on expression of BCRP, MRP2 and P-glycoprotein implicated in efflux of different ARV drugs. Darunavir strongly induced expression in most cell lines of CNT3 involved in cell uptake of nucleotide/nucleoside analogue reverse transcriptase inhibitors and SLCO drug transporters involved in cell uptake of protease inhibitors. This study provides insight into the suitability of cervicovaginal cell lines for assessment of ARV drugs in transport kinetics studies. The modulatory effect of darunavir and dapivirine on expression of drug transporters involved in transport of tenofovir points to the possibility of combining these drugs to improve retention of individual drugs at target tissues.

Bacillus spores for vaccine delivery.

Spores of the genus Bacillus have been used for a long time as probiotics for oral bacteriotherapy both in humans and in animals. Spores are also employed in a veterinary vaccine against anthrax. Despite this long lasting and extensive use, the specific contribution of spores to the beneficial effects of probiotics and to the immunogenicity of the vaccine is not completely elucidated. This review focuses on the different aspects of the use of spore preparations. In particular the use of recombinant spores as vaccine delivery vehicles is described and discussed.